Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkin's disease; there were no infective deaths in the absence of Hodgkin's disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkin's lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkin's disease.
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PMID:British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. 202 42

The addition of high-dose methylprednisolone (120 mg given i.v. and repeated after a 4-h interval) to a conventional antiemetic regimen consisting of metoclopramide (0.5 mg/kg given as an i.v. bolus over 30 min followed by 1 mg/kg given as a continuous infusion over 24 h) and alprazolam (0.5 mg given p.o.) was evaluated in a randomized study of leukemic patients undergoing anthracycline-containing multiple-day chemotherapy. Double-blind analysis was done in 30 patients who completed a total of 40 treatment courses. Cumulative 3-day results revealed complete control of nausea in 66% of patients and complete control of emesis in 77% of cases. The addition of methylprednisolone significantly reduced the occurrence of nausea (p = 0.003) and emesis (P = 0.06). Moreover, antiemetic rescue with chlorpromazine was less frequently necessary in patients receiving corticosteroids (P = 0.02). No harmful side effect was observed, and the incidence of severe infectious episodes was similar in both arms. We conclude that high-dose methylprednisolone can improve the efficacy of metoclopramide and alprazolam in controlling nausea and emesis induced by anthracycline-containing multiple-day chemotherapy in patients with acute myeloblastic leukemia.
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PMID:Antiemetic activity of high-dose methylprednisolone associated with continuous-infusion metoclopramide and oral alprazolam during multiple-day chemotherapy. 204 38

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
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PMID:Fludarabine: a review. 206 37

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

Seven patients with acute myeloid leukemia (AML) in first complete remission were treated with escalating high doses of cyclophosphamide, etoposide, and cytosine arabinoside (Ara-C). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored in blood bags in a refrigerator for 48-72 h at 4 degrees C and then reinfused over a central line. All patients had a full hematological recovery. The mean time of neutropenia (neutrophils less than 500/microliters) was 14 days (range 9-24 days), and the mean time of thrombocytopenia (platelets less than 20,000/microliters) was 9 days (range 7-11 days). The nonhematological toxicity was tolerable with mild to moderate nausea/vomiting, mucositis and diarrhea, and so far not dose-limiting. Six patients remain in complete remission 17+, 9+, 5+, 5+, 4+, and 1+ months after autotransplantation. One patient relapsed 8 months after autotransplantation. High-dose chemotherapy with noncryopreserved bone marrow autotransplantation may be useful as intensified consolidation for patients with AML in first complete remission.
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PMID:High-dose chemotherapy with noncryopreserved autologous bone marrow transplantation for acute myeloid leukemia in first complete remission. 232 69

Twenty-two evaluable adult patients with relapsed, acute nonlymphocytic leukemia (ANLL) were treated with the combination of amsacrine (m-AMSA) and 5-azacytidine (AZA) as part of an Eastern Cooperative Oncology Group (ECOG) pilot study to evaluate efficacy and toxicity. Each drug was given in a dosage of 150 mg/m2 i.v. daily for 5 consecutive days. A complete response (CR) was obtained in 8 of 22 patients (36%) and a partial response was seen in two others, yielding an overall response rate of 45%. Median survival for all 22 patients was 2.5 months, but medium survival was 7.2 months (range 4.3-13 months) for those with a CR. Twelve of 22 died during the first 3 months, seven of these during the period of drug-induced aplasia. Moderate to severe toxicity included serious infection (16 of 22); nausea, vomiting, and diarrhea (19 of 22); and mucositis (10 of 22). There were four instances each of cardiac abnormalities and hepatic abnormalities but all reversed spontaneously. We conclude that this combination therapy cannot be recommended for further investigation in relapsed patients with ANLL since there was no notable increase in long-term survival and since there were 10 treatment-related deaths out of 22 patients.
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PMID:Amsacrine [4'-(9-acridinylamino)-methanesulfon-m-anisidide] (m-AMSA) and 5-azacytidine (AZA) for remission reinduction in patients with relapsed adult acute nonlymphocytic leukemia. An ECOG pilot study. Eastern Cooperative Oncology Group. 243 42

From December, 1985 to October, 1987, 16 patients aged from 14 to 62 (median 34) with acute leukemia in relapse (10 affected by ANLL and 6 by ALL) were treated with the following regimen: Idarubicin 12 mg/m2/day on days 1-2-3, Ara-C 600 mg/m2 twice a day from day 1 to 6. Twelve patients (75%) achieved complete remission (C.R.). Two (12%) died during the induction phase from alveolar pneumonitis. One patient was resistant. The median duration of C.R. and survival was respectively 12 (range 6 to 100 +) and 23 weeks (4 to 108 +). The median duration of granulocytopenia was 16 days (range 10 to 24 days). The most frequent non-hematological complications consisted of nausea, vomiting, diarrhea and mucositis. Four patients had hepatic and splenic microabscesses of suspected mycotic etiology, and one showed a transient cardiac arrhythmia. The C.R. rate obtained in this series may be considered satisfaying since all but 3 patients were on treatment at the time of relapse. Yet the short duration of C.R. suggests the opportunity of performing consolidation cycles or suprelethal therapy followed by bone marrow transplantation.
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PMID:Idarubicin combined with intermediate-dose cytosine arabinoside in the treatment of refractory acute leukemia. 249 85

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.
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PMID:Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia. 253 73

We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
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PMID:4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia. 291 Apr 65

Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.
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PMID:Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia. 316


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